The overall goals are to understand the kinetics and control of neutrophilic leukocytes and hematopoietic stem cells (HSC). Our studies are described under 4 headings. 1) Proliferative potential of HSC, measured in in vivo assay systems, approaches the question of whether there is or is not a finite limit on the number of divisions of a normal HSC (in vivo cellular "aging"). The W/Wv has abnormal HSC but its hypoplastic anemia can be cured by infusing normal marrow, probably by infusion of only 1 appropriate HSC. Proliferative potential of infused marrow is studied by determining duration of cure of the W/Wv and transfer of that marrow to secondary, tertiary etc. other W/Wv and determining its production and maintenance of cure in them over many years. Other factors influencing this are studied such as proof of donor cells by chromosomal and hemoglobin analysis, role of thymocytes in cure and cure by fused cells. The nature of the anemia and neutrophilia, seen in seemingly normal, aged BDF1 mice, is under study for the same purposes. 2) Kinetics of Neutrophils in neutropenic patients; one major goal is to better characterize the various types of congenital neutropenia. In man and mouse, we wish to determine at what level of neutropenia the exudative neutrophil response becomes abnormal. 3) The hematopoietic microenvironment is studied utilizing such systems as the following: induction of hepatic hematopoiesis in adult mice; what does and doesn't induce it, its relationship to changes in Kupffer cells, production of stimulators and inhibitors of in vitro growth of HSC by various liver cells; the SL/SLd mouse has a defective microenvironment and with electron microscopic studies we are pursuing a possible "clue" to a defect in its macrophages; estrone induced osteosclerosis induces neutropenia which is disproportionate re changes in other blood cells and may represent a microenvironmental defect. 4) Recovery patterns following stem cell depletion; syngeneic marrow infusion into sub-lethally irradiated mice, including infusion of irradiated cells produced possible inhibition of erythropoietic recovery under certain circumstances. Resolution of the nature of this effect may be helpful as regards human autologous marrow transplant. Overall, these diverse studies should allow us to move toward a better understanding of the equally diverse factors whose interrelations result in maintenance of normal hematopoiesis.